- Origin and evolution of RNA and DNA viruses
- Virus taxonomy
- Molecular mechanisms of proteolytic processing in viruses
- Structure and function of nidovirus enzymes
RNA viruses, the largest group of viruses, cause many epidemic diseases in the human population, among crops and domestic livestock. These viruses possess an enormous potential to evolve quickly, due to low fidelity of viral RNA polymerases and high frequency of recombination. To safeguard human life in a world densely populated by ever-changing viruses, knowledge-based approaches for virus detection, discovery, cure and containment must be developed and implemented. Contributing toward these goals, we study the fundamentals of viruses, facilitate development of virus taxonomy, and advance diverse applications by applying bioinformatics to virus genome sequences. We reconstruct evolutionary relationships, physical interactions, and functional interplay among different viruses as well as between viral and cellular entities. In applied research, we seek to define targets for antivirus therapy and advance virus detection and discovery methods. We are developing a software platform for the efficient management and utilization of virus genome sequences and associated information in fundamental and applied research. Models developed in the course of our theoretical analyses have been successfully incorporated in other researchers' studies many of which have been conducted through fruitful collaboration.
Prof. Gorbalenya obtained Diploma in Biology (MS equivalent) with a specialization in cytology/genetics from Novosibirsk State University (Novosibirsk, USSR/Russia) in 1974. His Diploma Thesis was on the "Level of the corticosteroid hormones in plasma of inbred mice of low- and high-risk cancer lineages" (Supervisor: Dr. E.V. Gruntenko). In 1984 Alexander Gorbalenya was awarded with Candidate of Science Degree in Virology (PhD equivalent) from the Institute of Poliomyelitis & Viral Encephalitides (IPIVE), Academy of Medical Sciences, Moscow Region, USSR/Russia, for the biochemical discovery and characterization of the mouse encephalomyocarditis virus proteinase p22 - the first replicative protease that was identified in RNA viruses (Promotor: Prof. Vadim. I. Agol). In 1991, Dr. Gorbalenya was awarded with Doctor of Science Degree in Molecular Biology by Moscow State University (MSU), Moscow, USSR/Russia for the Thesis "Comparative amino acid sequence analysis for the purpose of functional dissection of viral proteins" in which he introduced the functional dissection of the RNA-virus proteome by means of bioinformatics. In 2011, Dr. Gorbalenya delivered professor inauguration lecture at the Leiden University with the title “Could we live in peace with viruses?”.
Starting from 1975, Dr. Gorbalenya has been working in virology mostly studying at the interface between evolution, structure and function of RNA viruses from genomics perspective by multidisciplinary approaches, including bioinformatics from 1982. These studies were conducted in the leading research Centres of Russia/USSR (Inst. of Mol. Biology, Koltsovo, and IPIVE; 1975-1998), the National Cancer Institute (Frederick, MD, USA; 1998-2001), and since December 2001 at LUMC in Leiden. In USSR/Russia, Alexander Gorbalenya started his career as an engineer (1974) and grew through ranks to head a group at the Institute of Molecular Biology in 1978, and to found one of the first bioinformatics groups (1984) and be promoted to a tenured lead research scientist at the IPIVE (1991-1998). During the 1990s, Dr. Gorbalenya was a visiting scientist/professor in laboratories of Prof. Michael Rossmann (Purdue University, W.Lafayette, IN, USA), Prof. Willy Spaan (Leiden University) and Prof. Stuart Siddell (Wuerzburg University, Wuerzburg, Germany). From December 2001 till June 2009 he was a tenured Associate Professor, and since July 1st, Leiden University Fund Professor of Applied Bioinformatics in Virology at the Department of Medical Microbiology. In October 2004, Dr. Gorbalenya was appointed to head a joint bioinformatics group between LUMC and Moscow State University (MoBiLe – Moscow-Bioinformatics-Leiden) at the A.N. Belozersky Inst.of Physico-Chemical Biology, Moscow, and in September 2007, he was appointed a Professor at Faculty of Bioengineering and Bioinformatics, Moscow State University.
Prof. Gorbalenya is a Co-organizer of a month-long Summer School in Bioinformatics at LUMC for top undergraduate students of the Faculty of Bioengineering and Bioinformatics, Moscow State University. Since 2005, 131 students have conducted research projects at LUMC, with 22 of them working in the Gorbalenya group. Prof. Gorbalenya was a promoter for 14 Masters and 5 PhD students whose projects were defended at MSU and LUMC, respectively. He was invited to evaluate and/or advice on several PhD projects defended in the USSR/Russia, India, Finland, UK, and the Netherlands. Prof. Gorbalenya has contributed with state-of-the-art lectures to several teaching programs at LUMC and abroad.
Research of Prof. Gorbalenya has been documented in more than 200 peer-reviewed original publications, reviews and book chapters written in the English and Russian. He was invited to present results at numerous international and national conferences, and to give dozens seminars at leading Institutions in Europe, Japan, Russia, Singapore, and the USA.
Prof. Gorbalenya's research is/was supported by the RFFR, the NWO, the NBIC and the EU. He is a PI in the EU projects EVAg (2015-2019) and Zikaliance (2016-2020). He was a PI of the SILVER project (2009-2014) and Workpackage/Section leader for the EU VIZIER project (2004-2009), NBIC BioRange project (2005-2011), EU GRACE project (2006-2011); in the EUVIRNA (2011-2014), VIZIER and GRACE projects he serve(d) at the Steering/Executive Committee.
Prof. Gorbalenya is Editor of Virology since 2013, and serves on the Editorial Boards of J. of Virology and Virus Research. He was Guest Editor of Proc.Natl.Acad.Sci. USA and PLoS Pathogens, and Editorial Board Member of J. of General Virology. He served at the Advisory Panel for the Virus Genomes Database of NCBI (USA), the Advisory Board for the XVth and XVIth International Congresses of Virology (2011 and 2014), and several other international committees and boards concerned with viruses and bioinformatics. He was an ad-hoc reviewer for dozens of international journals as well as for grant agencies in the Netherlands, EU, France, Israel, UK and Russia. From 2005 till 2011 he served as an elected member of the Executive Committee and from 2011 to 2017 as Vice-President of the International Committee for Taxonomy of Viruses. Prof. Gorbalenya was a co-organizer of several international Symposiums and Workshops, most recently Europic2018 to be held in the Netherlands, June, 2018, and he was invited to (co-)chair sessions at international meetings, including International Congresses of Virology.
Lehmann KC, Gulyaeva A, Zevenhoven-Dobbe JC, Janssen GM, Ruben M, Overkleeft HS, van Veelen PA, Samborskiy DV, Kravchenko AA, Leontovich AM, Sidorov IA, Snijder EJ, Posthuma CC, Gorbalenya AE. Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses. Nucleic Acids Res. 2015; 43:8416-34.
Lauber C, Kazem S, Kravchenko AA, Feltkamp MC, Gorbalenya AE. Interspecific adaptation by binary choice at de novo polyomavirus T antigen site through accelerated codon-constrained Val-Ala toggling within an intrinsically disordered region. Nucleic Acids Res. 2015;43(10):4800-13.
Lauber C, Goeman JJ, Parquet MDC, Nga PT, Snijder EJ, Morita K, Gorbalenya AE. The footprint of genome architecture in the largest genome expansion in RNA viruses. PLoS Pathog. 2013; 9(7):e1003500.
Lauber C, Gorbalenya AE. Toward Genetics-Based Taxonomy: Comparative Analysis of a Genetics-Based Classification and the Taxonomy of Picornaviruses. J Virol.2012; 86: 3905-15.
Nga PT, Parquet MDC, Lauber C, Parida M, Nabeshima T, Yu F, Thuy NT, Inoue S, Ito T, Okamoto K, Ichinose A, Snijder EJ, Morita K, Gorbalenya AE. Discovery of the first insect nidovirus, a missing evolutionary link in the emergence of the largest RNA virus genomes. PLoS Pathog. 2011; 7:e1002215.
Gorbalenya AE, Lieutaud P, Harris M, CoutardB, Canard B, Kleywegt GK, Kravchenko AA, Samborskiy DV, Sidorov IA, Leontovich AM, Jones TA. Practical application of bioinformatics by the multidisciplinary VIZIER consortium. Antiviral Res. 2010;@87: 95-110.
van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Pathog. 2010; 6:e1001024.
Le Gall O, Christian P, Fauquet C, King A, KnowlesNJ, Nakashima N, Stanway G, Gorbalenya AE. Picornavirales, a proposed order of positive-sense single-stranded RNA viruses with a pseudo T=3 virion architecture. Arch of Virol. 2008; 153:715-27.
Jiang P, Faase JAJ, Toyoda H, Paul A, Wimmer E, Gorbalenya AE. Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradication. Proc Natl Acad Sci USA. 2007; 104:9457-62.
Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res. 2006; 117:17-37.
Minskaia E, Hertzig T, Gorbalenya AE, Campanacci V, Cambillau C, Canard B, Ziebuhr J. Discovery of an RNA virus 3'->5' exoribonuclease that is critically involved in coronavirus RNA synthesis. Proc Natl Acad Sci USA. 2006; 103: 5108-13.
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